The purpose of this project is to study the role of the immune system in connective tissue metabolism. Experiments with the osteopetrotic (op) rat have revealed that lymphocytes from these animals are suppressed in their proliferative responses and the macrophages are defective in chemotaxis. However, the lymphocyte from the op rat produces normal levels of chemotactic factor, the monocytes produce normal levels of lymphocyte activating factor and PGE2. The possible role of macrophages in streptococcal cell wall (STC CW) induced adjuvant arthritis in rats was examined by obtaining peritoneal macrophages from Lewis (susceptible) or Fisher (resistant) rats at various times after injection of STCCW. Macrophages from STCCW injected Fisher rats produced more PGE2 than the non-injected controls while there was no difference in macrophage PGE2 production between control and injected Lewis rats. However macrophages from Lewis rats produced significantly less PGE2 than macrophages from Fisher rats. In studies dealing with peripheral blood cells from normal volunteers and rheumatoid arthritis patients we have modified the technique of counterflow centrifuge elutriation to separate large numbers of B cells, T cells and monocytes into relatively pure populations.